Electrocatalytic Conversion of CO2 to Formic Acid: A Journey from 3d-Transition Metal-Based Molecular Catalyst Design to Electrolyzer Assembly.

ConspectusElectrochemical CO2 reduction to obtain formate or formic acid is receiving significant attention as a method to combat the global warming crisis. Significant efforts have been devoted to the advancement of CO2 reduction techniques over the past few decades. This Account provides a unified discussion on various electrochemical methodologies for CO2 to formate conversion, with a particular focus on recent advancements in utilizing 3d-transition-metal-based molecular catalysts. This Account primarily focuses on understanding molecular functions and mechanisms under homogeneous conditions, which is essential for assessing the optimized reaction conditions for molecular catalysts. The unique architectural features of the formate dehydrogenase (FDH) enzyme provide insight into the key role of the surrounding protein scaffold in modulating the active site dynamics for stabilizing the key metal-bound CO2 intermediate. Additionally, the protein moiety also triggers a facile proton relay around the active site to drive electrocatalytic CO2 reduction forward. The fine-tuning of FDH machinery also ensures that the electrocatalytic CO2 reduction leads to the production of formic acid as the major yield without any other carbonaceous products, while limiting the competitive hydrogen evolution reaction. These lessons from the enzymes are key in designing biomimetic molecular catalysts, primarily based on multidentate ligand scaffolds containing peripheral proton relays. The subtle modifications of the ligand framework ensure the favored production of formic acid following electrocatalytic CO2 reduction in the solution phase. Next, the molecular catalysts are required to be mounted on robust electroactive surfaces to develop their corresponding heterogeneous versions. The surface-immobilization provides an edge to the molecular electrocatalysts as their reactivity can be scaled up with improved durability for long-term electrocatalysis. Despite challenges in developing high-performance, selective catalysts for the CO2 to formic acid transformation, significant progress is being made with the tactical use of graphene and carbon nanotube-based materials. To date, the majority of the research activity stops here, as the development of an operational CO2 to formic acid converting electrolyzer prototype still remains in its infancy. To elaborate on the potential future steps, this Account covers the design, scaling parameters, and existing challenges of assembling large-scale electrolyzers. A short glimpse at the utilization of electrolyzers for industrial-scale CO2 reduction is also provided here. The proper evaluation of the surface-immobilized electrocatalysts assembled in an electrolyzer is a key step for gauging their potential for practical viability. Here, the key electrochemical parameters and their expected values for industrial-scale electrolyzers have been discussed. Finally, the techno-economic aspects of the electrolyzer setup are summarized, completing the journey from tactical design of molecular catalysts to their appropriate application in a commercially viable electrolyzer setup for CO2 to formate electroreduction. Thus, this Account portrays the complete story of the evolution of a molecular catalyst to its sustainable application in CO2 utilization.

Green H2 Generation from Seawater Deploying a Bifunctional Hetero-Interfaced CoS2-CoFe-Layered Double Hydroxide in an Electrolyzer.

This work illustrates the practicality and economic benefits of employing a hetero-interfaced electrocatalyst (CoS2@CoFe-LDH), containing cobalt sulphide and iron-cobalt double-layer hydroxide for large-scale hydrogen generation. Here, the rational synthesis and detailed characterization of the CoS2@CoFe-LDH material to unravel its unique heterostructure are essayed. The CoS2@CoFe-LDH operates as a bifunctional electrocatalyst to trigger both the hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER) in alkaline seawater (pH 14.0) while showcasing low overpotential requirement for HER (311 mV) and OER (450 mV) at 100 mA cm- 2 current density. The identical CoS2@CoFe-LDH on either electrode in an H-cell setup results in simultaneous H2 and O2 production from seawater with a ≈98% Faradaic efficiency with an applied potential of 1.96V@100 mA cm- 2. Next, this CoS2@CoFe-LDH catalyst is deployed on both sides of a membrane electrode assembly in a one-stack electrolyzer, which retains the intrinsic bifunctional reactivity of the catalyst to generate H2 and O2 in tandem from alkaline seawater with an impeccable energy efficiency (50 kWh kg-1-of-H2). This electrolyzer assembly can be directly linked with a Si-solar cell to produce truly green hydrogen with a solar-to-hydrogen generation efficiency of 15.88%, highlighting the potential of this converting seawater to hydrogen under solar irradiation.

Expedited Proton Relay in Enzyme-Inspired Cobaloximes Facilitate Organic Transformations.

Developing a water-soluble, oxygen-tolerant, and acid-stable synthetic H2 production catalyst is vital for renewable energy infrastructure. To access such an effective catalyst, we strategically incorporated enzyme-inspired, multicomponent outer coordination sphere elements around the cobaloxime (Cl-Co-X) core with suitable axial coordination (X). Our cobaloximes with axial imidazole or L-histidine coordination in photocatalytic HAT including the construction of anilines via a non-canonical cross-coupling approach is found superior compared to commonly used cobaloxime catalysts. The reversible Co(II)/Co(I) process is influenced by the axial N ligand's nature. Imidazole/L-histidine with a higher pKa promptly produces H2 upon irradiation, leading to the improved reactivity compared to previously employed axial (di)chloride or pyridine analogue.

Highly Stable Self-Regenerating Organic Multi-Redox Systems derived from Bicyclic (Alkyl)(amino)carbenes (BICAACs).

An extended class of organic multi-redox systems was derived from bicyclic(alkyl)amino carbenes (BICAACs). The highly-conjugated system undergoes a total of 4 redox events spanning a 1.8 V redox range. These organic compounds exhibited four different stable redox states (dication, radical cation, neutral and radical anion), and all of them were characterized either by single crystal X-ray study and/or various spectroscopic studies. Three of the four redox states are stable to air and moisture. The availability of stable multiple redox states demonstrated promise towards their efficacy in the symmetric H-cell charge/discharge cycling. Among various redox states, the dication/neutral state works efficiently and continuously for 1500 cycles in 2e- charge/discharge process outside glovebox in commercially available DMF with minimum capacity loss (retaining nearly 90 % Coulombic efficiency). Surprisingly, the efficiency of the redox cycle was retained even if the system was exposed to air for 30 days when it slowly regenerated to the initial deep blue radical cation, and it exhibited another 100 charge/discharge cycles with a minimal capacity loss. Such a stable H-cell cycling ability is not well known among organic molecule-based systems.

Beyond S and Se: Electrocatalytic Hydrogen Production by Tellurolate-Bridged Co(III)-Mn(I) Heterodinuclear Complexes.

In the pursuit of efficient electrocatalysts for the hydrogen evolution reaction (HER), a series of manganese and cobalt heterodinuclear complexes have been synthesized and characterized that have a stark resemblance with the [NiFe]-hydrogenase active site structure. Irradiation of [Mn2(CO)10] in the presence of 1.5 eq of [NaEPh] [E = S, Se, Te] followed by reaction with [Cp*CoCl]2 led to the formation of half-sandwiched trichalcogenate-bridged heterodinuclear complexes [{Mn(CO)3}(µ-EPh)3(CoCp*)] [E = S (C1); Se (C2) and Te (C3)]. The reaction of these heterodinuclear trichalcogenate-bridged complexes with [LiBH4·THF] yielded the corresponding dichalcogenate hydride-bridged heterobimetallic complexes [(CO)3Mn(µ-EPh)2(µ-H)(CoCp*)] [E = S (C5); Se (C6) and Te (C7)], which closely imitate the Ni-R intermediate of [NiFe]-hydrogenase. The resultant complexes (C5-C7) displayed impressive H2 production in DMF in the presence of HBF4, whereas the Te-based complex (C7) showcased the highest TON (184 h-1) with an impressive Faradaic efficiency of >98%. The DFT investigations revealed a unique role of bridging chalcogens in catalysis, wherein, depending on the identity of the chalcogen (S, Se, or Te), protonation could occur via two distinct routes. This study represents a rare example of the full trio of S/Se/Te-based heterodinuclear complexes whose electrocatalytic HER activity has been probed under analogous conditions.

Green Light-Triggered Photocatalytic Anticancer Activity of Terpyridine-Based Ru(II) Photocatalysts.

The relentless increase in drug resistance of platinum-based chemotherapeutics has opened the scope for other new cancer therapies with novel mechanisms of action (MoA). Recently, photocatalytic cancer therapy, an intrusive catalytic treatment, is receiving significant interest due to its multitargeting cell death mechanism with high selectivity. Here, we report the synthesis and characterization of three photoresponsive Ru(II) complexes, viz., [Ru(ph-tpy)(bpy)Cl]PF6 (Ru1), [Ru(ph-tpy)(phen)Cl]PF6 (Ru2), and [Ru(ph-tpy)(aip)Cl]PF6 (Ru3), where, ph-tpy = 4'-phenyl-2,2':6',2″-terpyridine, bpy = 2,2'-bipyridine, phen = 1,10-phenanthroline, and aip = 2-(anthracen-9-yl)-1H-imidazo[4,5-f][1,10] phenanthroline, showing photocatalytic anticancer activity. The X-ray crystal structures of Ru1 and Ru2 revealed a distorted octahedral geometry with a RuN5Cl core. The complexes showed an intense absorption band in the 440-600 nm range corresponding to the metal-to-ligand charge transfer (MLCT) that was further used to achieve the green light-induced photocatalytic anticancer effect. The mitochondria-targeting photostable complex Ru3 induced phototoxicity with IC50 and PI values of ca. 0.7 µM and 88, respectively, under white light irradiation and ca. 1.9 µM and 35 under green light irradiation against HeLa cells. The complexes (Ru1-Ru3) showed negligible dark cytotoxicity toward normal splenocytes (IC50s > 50 µM). The cell death mechanistic study revealed that Ru3 induced ROS-mediated apoptosis in HeLa cells via mitochondrial depolarization under white or green light exposure. Interestingly, Ru3 also acted as a highly potent catalyst for NADH photo-oxidation under green light. This NADH photo-oxidation process also contributed to the photocytotoxicity of the complexes. Overall, Ru3 presented multitargeting synergistic type I and type II photochemotherapeutic effects.

Polypyridyl CoII -Curcumin Complexes as Photoactivated Anticancer and Antibacterial Agents.

Four new CoII complexes, [Co(bpy)2 (acac)]Cl (1), [Co(phen)2 (acac)]Cl (2), [Co(bpy)2 (cur)]Cl (3), [Co(phen)2 (cur)]Cl (4), where bpy=2,2'-bipyridine (1 and 3), phen=1,10-phenanthroline (2 and 4), acac=acetylacetonate (1 and 2), cur=curcumin monoanion (3 and 4) have been designed, synthesized and fully characterized. The X-ray crystal structures of 1 and 2 indicated that the CoN4 O2 core has a distorted octahedral geometry. The photoactivity of these complexes was tuned by varying the π conjugation in the ligands. Curcumin complexes 3 and 4 had an intense absorption band near 435 nm, which made them useful as visible-light photodynamic therapy agents; they also showed fluorescence with λem ≈565 nm. This fluorescence was useful for studying their intracellular uptake and localization in MCF-7 breast cancer cells. The acetylacetonate complexes (1 and 2) were used as control complexes to understand the role of curcumin. The white-light-triggered anticancer profiles of the cytosol targeting complexes 3 and 4 were investigated in detail. These non-dark toxic complexes displayed significant apoptotic photo-cytotoxicity (under visible light) against MCF-7 cells through ROS generation. The control complexes 1 and 2 did not induce significant cell death in the light or dark. Interestingly, 1-4 produced a remarkable antibacterial response upon light exposure. Overall, the reported results here can increase the boundary of the CoII -based anticancer and antibacterial drug development.

Expanding the Horizon of Bio-Inspired Catalyst Design with Tactical Incorporation of Drug Molecules.

The development of potent H2 production catalysts is a key aspect in our journey toward the establishment of a sustainable carbon-neutral power infrastructure. Hydrogenase enzymes provide the blueprint for designing efficient catalysts by the rational combination of central metal core and protein scaffold-based outer coordination sphere (OCS). Traditionally, a biomimetic catalyst is crafted by including natural amino acids as OCS features around a synthetic metal motif to functionally imitate the metalloenzyme activity. Here, we have pursued an unconventional approach and implanted two distinct drug molecules (isoniazid and nicotine hydrazide) at the axial position of a cobalt core to create a new genre of synthetic catalysts. The resultant cobalt complexes are active for both electrocatalytic and photocatalytic H2 production in near-neutral water, where they significantly enhance the catalytic performance of the unfunctionalized parent cobalt complex. The drug molecules showcased a dual effect as they influence the catalytic HER by improving the surrounding proton relay along and exerting subtle electronic effects. The isoniazid-ligated catalyst C1 outperformed the nicotine hydrazide-bound complex C2, as it produced H2 from water (pH 6.0) at a rate of 3960 s-1 while exhibiting Faradaic efficiency of about 90 %. This strategy opens up newer avenues of bio-inspired catalyst design beyond amino acid-based OCS features.

Combined charge and hydrophobicity-guided screening of antibacterial peptides: two-level approach to predict antibacterial activity and efficacy.

Antibacterial peptides can be a potential game changer in the fight against antibiotic resistance. In order for these peptides to become successful antibiotic alternatives, it is essential that they possess high efficacy in addition to just being antibacterial. In this study, we have developed a two-level SVM-based binary classification approach to predict the antibacterial activity of a given peptide (model 1) and thereafter classify its antibacterial efficacy as high/low (model 2) with respect to minimum inhibitory concentration (MIC) values against Staphylococcus aureus, one of the most common pathogens. Based on charge and hydrophobicity of amino acids, we developed a sequence-based combined charge and hydrophobicity-guided triad (CHT) as a new method for obtaining features of any peptide. Model 1 with a combination of CHT and amino acid composition (AAC) as the feature representation method resulted in the highest accuracy of 96.7%. Model 2 with CHT as the feature representation method yielded the highest accuracy of 70.9%. Thus, CHT is found to be a potential feature representation method for classifying antibacterial peptides based on both activity and efficacy. Furthermore, we have also used an explainable machine learning algorithm to extract various insights from these models. These insights are found to be in excellent agreement with experimental findings reported in the literature, thus enhancing the dependability of the proposed models.

Role of Partial Vacancy and Structural Distortion in the Stability of Nonstoichiometric Phases Ni7-δInSe2-xSx (1.26 ≥ δ ≥ 0.94; 0 ≤ x ≤ 1.33).

This study explores the structure and stability of partly disordered sulfur-substituted Ni5.74InSe2 (I4/mmm, a = 3.6766(1) Å, c = 18.8178(10) Å, Z = 2). The structure of Ni7-δInSe2-xSx (x = 0.2, 0.36, 0.66, 0.80, 0.94) compounds is isotypic to their parent Ni5.74InSe2 and can be viewed as alternating heterometallic Cu3Au-type ∞2[Ni3In] slabs and defective Cu2Sb-type ∞2[Ni4-δ(Se/S)2] slabs along the [001]-axis. Similar to the parent Se-compound, the Ni-Ch (Ch = chalcogen) fragment is non-stoichiometric and possesses a partially occupied Ni-site. It was observed that with sulfur insertion at the selenium site of Ni5.74InSe2, the interatomic distance between the partially occupied nickel and mixed (S/Se) sites decreases from ∼2.24 to ∼1.95 Å, and the occupancy of the disordered nickel site simultaneously increases. The limiting composition Ni6.06InSe0.67S1.33 (x = 1.33, δ = 0.94) is formed in the sulfur-rich region. Its average structure resembles the Ni6SnS2-type and has a similar motif to Ni5.74InSe2; the only difference is that Cu3Au-type ∞2[Ni3In] alternates with two types of Ni-Ch fragments (Cu2Sb or Li2O type units). By using first-principles electronic structure calculations, we explained the presence of partially disordered nickel sites in the Ni-Ch fragment and rationalized why the nickel site occupancy increases with sulfur insertion.

Cu4TiTe4: Synthesis, Crystal Structure, and Chemical Bonding.

A new compound Cu4TiTe4 in the Cu-Ti-Te ternary system is prepared using high-temperature solid-state synthesis and characterized by single-crystal X-ray diffraction and energy-dispersive X-ray spectroscopy. The average structure of Cu4TiTe4 crystallizes in the cubic space group P4̅3m (cP9; a = 5.9484(1) Å) and adopts the Cu4TiSe4 structure type. Like Cu4TiSe4, it shows positional disorder in one of the two Cu sites. The three-dimensional structure of Cu4TiTe4 is viewed as a cubic close-packed (ccp) array of Te, where half of the tetrahedral holes are orderly occupied by three Cu and one Ti and the disordered Cu atoms effectively occupied 1/4 of the octahedral holes. The calculated density of states (DOS) discerns that the compound is a narrow-bandgap semiconductor, and the crystal orbital Hamilton population (COHP) analysis shows that though the individual Cu-Te short contact is relatively weak compared to the Ti-Te contact, Cu-Te bonds largely contribute toward the overall stability. Due to the unique atomic arrangements, some Te atoms in the unit cell have unsaturated coordination, which presents 5s2 lone pairs on the Te atoms. This has been confirmed by the density of states (DOS) and electron localization function (ELF) calculations.

3,6,13,16-Tetrapropylporphycene: Rational Synthesis, Complexation, and Halogenation.

We have designed and synthesized 3,6,13,16-tetrapropylporphycene for the first time as its alkyl analogue from ethyl 4-propyl-1H-pyrrole-2-carboxylate. The substituent effect was found to be more intense than reported positional isomeric tetrapropylporphycenes. The freebase porphycene exhibited moderate fluorescence and complexation ability with divalent metal ions, including Zn(II), which displayed an enhanced emission quantum yield (∼30%). The Pd(II) complex and freebase ß-tetrabromoporphycene generated singlet oxygen efficiently (75 and 51%, respectively) and, hence, may find application as potential photosensitizers in photodynamic therapy.

Redox-Induced Intramolecular C-C Coupling of Acyclic Bis(2-pyridylmethylene)ethylenediamine on a Ru(acac)2 Platform.

The paper documents redox-triggered C-C coupling of acyclic N,N'-bis(2-pyridylmethylene)ethylenediamine (BPE) to yield 2,3-bis(2-pyridyl)pyrazine (DPP) upon coordination to an electron-rich {Ru(acac)2} (acac = acetylacetonate) unit. This led to DPP-bridged [{Ru(acac)2}2(DPP)]0/+ (2 and [2]ClO4) along with the unperturbed BPE-bridged [{Ru(acac)2}2(BPE)] (1). On the contrary, electron-poor {Ru(Cl)(H)(CO)(PPh3)3} yielded BPE-bridged [3](ClO4)2 as an exclusive product. Synergistic metal (Ru)-ligand (BPE) redox participation toward chemical noninnocence of the Schiff base ligand and DPP-mediated electronic communication in RuIIRuIII-derived [2]ClO4 are addressed.

Nonconjugated Biocompatible Macromolecular Luminogens for Sensing and Removals of Fe(III) and Cu(II): DFT Studies on Selective Coordination(s) and On-Off Sensing.

This work reports the design and synthesis of two nonaromatic biocompatible macromolecular luminogens, i.e., 2-(dimethylamino)ethyl methacrylate-co-2-(dimethylamino)ethyl 3-(N-(methylol)acrylamido)-2-methylpropanoate-co-N-(methylol)acrylamide/DMAEMA-co-DMAENMAMP-co-NMA (P1) and methacrylic acid-co-3-(N-(methylol)acrylamido)-2-methylpropanoic acid-co-N-(methylol)acrylamide/MEA-co-NMAMPA-co-NMA (P2), prepared through in situ anchored acrylamido-ester/DMAENMAMP and acrylamido-acid/NMAMPA third comonomers, respectively, in a facile polymerization of two non-luminous monomers in water medium to circumvent the drawbacks related to aggregation-caused quenching of aromatic luminogens. The structures of P1/P2, in situ anchored comonomers, fluorophores, N-branching associated n-π* interactions, and hydrogen bonding assisted aggregation-enhanced emissions are comprehended by nuclear magnetic resonance, Fourier transform infrared (FTIR), X-ray photoelectron spectroscopy (XPS), ultraviolet-visible, thermogravimetric analysis (TGA), dynamic light scattering (DLS), transmission electron microscopy (TEM), fluorescence lifetime, and fluorescence imaging. P1 and P2 are appropriate for sensitive detections/exclusions of Fe(III)/Cu(II) and cell-imaging. The intrinsic fluorescence, on-off sensing, selective coordinations of Fe(III) and Cu(II) with fluorophores, emission quenching mechanisms, and removals of Fe(III) and Cu(II) are investigated by DFT/NTO analyses of P1/P2 and Fe(III)-P1 and Cu(II)-P2 complexes, XPS, and isotherms and kinetics parameters. The excellent biocompatibilities, comparable limit of detections, i.e., 1.70 × 10-7 and 1.59 × 10-7 [m], and higher adsorption capacities, i.e., 77.25 and 154.13 mg g-1 , at low ppm; 303 K; and pH = 7 compel P1/P2 to be acceptable for multipurpose applications.

Multi-C-C/C-N-Coupled Light-Emitting Aliphatic Terpolymers: N-H-Functionalized Fluorophore Monomers and High-Performance Applications.

To circumvent costly fluorescent labeling, five nonconventional, multifunctional, intrinsically fluorescent aliphatic terpolymers (1-5) have been synthesized by C-C/C-N-coupled, solution polymerization of two non-emissive monomers with protrusions of fluorophore monomers generated in situ. These scalable terpolymers were suitable for sensing and high-performance exclusion of CuII , logic function, and bioimaging. The structures of the terpolymers, in situ attachment of fluorescent monomers, aggregation-induced enhanced emission, bioimaging ability, and super adsorption were investigated by 1 H and 13 C NMR, EPR, FTIR, X-ray photoelectron, UV/Vis, and atomic absorption spectroscopy, thermogravimetric analysis, high-resolution transmission electron microscopy, dynamic light scattering, solid-state fluorescence, fluorescence imaging, and fluorescence lifetime measurements, as well as by isotherm, kinetics, and thermodynamic studies. The geometries and electronic structures of the fluorophores and the absorption and emission properties of the terpolymers were examined by DFT, time-dependent DFT, and natural transition orbital analyses. For 1, 2, and 5, the limits of detection were determined to be 1.03×10-7 , 1.65×10-7 , and 1.77×10-7 m, respectively, and the maximum adsorption capacities are 1575.21, 1433.70, and 1472.21 mg g-1 , respectively.

Synthesis of Biocompatible Aliphatic Terpolymers via In Situ Fluorescent Monomers for Three-in-One Applications: Polymerization of Hydrophobic Monomers in Water.

Biocompatible, nonconventional, multifunctional, purely aliphatic, light-emitting terpolymers, i.e., acrylonitrile-co-3-(N-isopropylacrylamido)propanenitrile-co-N-isopropylacrylamide (AN-co-NIPAMPN-co-NIPA, 1) and acrylonitrile-co-3-(N-hydroxymethylacrylamido)propanenitrile-co-N-hydroxymethylacrylamide (AN-co-NHMAMPN-co-NHMA, 2), were designed and synthesized via N-H-functionalized C-C + N-C-coupled in situ protrusions/grafting of fluorophore monomers, i.e., NIPAMPN and NHMAMPN, by solution polymerization of two highly hydrophobic nonemissive monomers in water. These scalable and reusable 1 and 2 were suitable for high-performance three-in-one applications, such as Fe(III) sensors, imaging of Madin-Darby canine kidney (MDCK) and human lung cancer (A549) cells, and security inks. The structures of 1 and 2, N-C-coupled in situ attachments/grafting of third fluorophore monomers, grafting events, and aggregation-enhanced emissions (AEEs), were analyzed by 1H and 13C NMR spectroscopy, X-ray photoelectron spectroscopy (XPS), Fourier transform infrared (FTIR) spectroscopy, ultraviolet-visible (UV-vis) spectroscopy, thermogravimetric (TG) analysis, high-resolution transmission electron microscopy (HRTEM), dynamic light scattering (DLS), fluorescence imaging, and fluorescence lifetime. The geometries, electronic structures, and absorption/emission properties of 1 and 2 at optimized compositions were examined by density functional theory (DFT), time-dependent DFT (TDDFT), and natural transition orbital (NTO) analyses. The limits of detection were 3.20 × 10-7 and 1.37 × 10-7 M for 1 and 2, respectively. The excellent biocompatibility of 1 and 2 was confirmed by >95% retention of MDCK and A549 cell morphologies.

Amino acid modified Ni catalyst exhibits reversible H2 oxidation/production over a broad pH range at elevated temperatures.

Hydrogenases interconvert H2 and protons at high rates and with high energy efficiencies, providing inspiration for the development of molecular catalysts. Studies designed to determine how the protein scaffold can influence a catalytically active site have led to the synthesis of amino acid derivatives of [Ni(P2(R)N2(R'))2](2+) complexes, [Ni(P2(Cy)N2(Amino acid))2](2+) (CyAA). It is shown that these CyAA derivatives can catalyze fully reversible H2 production/oxidation at rates approaching those of hydrogenase enzymes. The reversibility is achieved in acidic aqueous solutions (pH = 0-6), 1 atm 25% H2/Ar, and elevated temperatures (tested from 298 to 348 K) for the glycine (CyGly), arginine (CyArg), and arginine methyl ester (CyArgOMe) derivatives. As expected for a reversible process, the catalytic activity is dependent upon H2 and proton concentrations. CyArg is significantly faster in both directions (∼300 s(-1) H2 production and 20 s(-1) H2 oxidation; pH = 1, 348 K, 1 atm 25% H2/Ar) than the other two derivatives. The slower turnover frequencies for CyArgOMe (35 s(-1) production and 7 s(-1) oxidation under the same conditions) compared with CyArg suggests an important role for the COOH group during catalysis. That CyArg is faster than CyGly (3 s(-1) production and 4 s(-1) oxidation) suggests that the additional structural features imparted by the guanidinium groups facilitate fast and reversible H2 addition/release. These observations demonstrate that outer coordination sphere amino acids work in synergy with the active site and can play an important role for synthetic molecular electrocatalysts, as has been observed for the protein scaffold of redox active enzymes.

Carbon-Nanotube-Supported Bio-Inspired Nickel Catalyst and Its Integration in Hybrid Hydrogen/Air Fuel Cells.

A biomimetic nickel bis-diphosphine complex incorporating the amino acid arginine in the outer coordination sphere was immobilized on modified carbon nanotubes (CNTs) through electrostatic interactions. The functionalized redox nanomaterial exhibits reversible electrocatalytic activity for the H2 /2 H+ interconversion from pH 0 to 9, with catalytic preference for H2 oxidation at all pH values. The high activity of the complex over a wide pH range allows us to integrate this bio-inspired nanomaterial either in an enzymatic fuel cell together with a multicopper oxidase at the cathode, or in a proton exchange membrane fuel cell (PEMFC) using Pt/C at the cathode. The Ni-based PEMFC reaches 14 mW cm-2 , only six-times-less as compared to full-Pt conventional PEMFC. The Pt-free enzyme-based fuel cell delivers ≈2 mW cm-2 , a new efficiency record for a hydrogen biofuel cell with base metal catalysts.

Investigating the role of chain and linker length on the catalytic activity of an H2 production catalyst containing a ß-hairpin peptide.

Building on our recent report of an active H2 production catalyst [Ni(PPh 2NProp-peptide)2]2+ (Prop = para-phenylpropionic acid, peptide (R10) = WIpPRWTGPR-NH2, p = D-proline and P2N = 1-aza-3,6-diphosphacycloheptane) that contains structured ß-hairpin peptides, here we investigate how H2 production is effected by: (1) the length of the hairpin (eight or ten residues) and (2) limiting the flexibility between the peptide and the core complex by altering the length of the linker: para-phenylpropionic acid (three carbons) or para-benzoic acid (one carbon). Reduction of the peptide chain length from ten to eight residues increases or maintains the catalytic current for H2 production for all complexes, suggesting a non-productive steric interaction at longer peptide lengths. While the structure of the hairpin appears largely intact for the complexes, NMR data are consistent with differences in dynamic behavior which may contribute to the observed differences in catalytic activity. Molecular dynamics simulations demonstrate that complexes with a one-carbon linker have the desired effect of restricting the motion of the hairpin relative to the complex; however, the catalytic currents are significantly reduced compared to complexes containing a three-carbon linker as a result of the electron withdrawing nature of the -COOH group. These results demonstrate the complexity and interrelated nature of the outer coordination sphere on catalysis.

Beyond the active site: the impact of the outer coordination sphere on electrocatalysts for hydrogen production and oxidation.

Redox active metalloenzymes play a major role in energy transformation reactions in biological systems. Examples include formate dehydrogenases, nitrogenases, CO dehydrogenase, and hydrogenases. Many of these reactions are also of interest to humans as potential energy storage or utilization reactions for photoelectrochemical, electrolytic, and fuel cell applications. These metalloenzymes consist of redox active metal centers where substrates are activated and undergo transformation to products accompanied by electron and proton transfer to or from the substrate. These active sites are typically buried deep within a protein matrix of the enzyme with channels for proton transport, electron transport, and substrate/product transport between the active site and the surface of the protein. In addition, there are amino acid residues that lie in close proximity to the active site that are thought to play important roles in regulating and enhancing enzyme activity. Directly studying the outer coordination sphere of enzymes can be challenging due to their complexity, and the use of modified molecular catalysts may allow us to provide some insight. There are two fundamentally different approaches to understand these important interactions. The "bottom-up" approach involves building an amino acid or peptide containing outer coordination sphere around a functional molecular catalyst, and the "top-down" approach involves attaching molecular catalyst to a structured protein. Both of these approaches have been undertaken for hydrogenase mimics and are the emphasis of this Account. Our focus has been to utilize amino acid or peptide based scaffolds on an active functional enzyme mimic for H2 oxidation and production, [Ni(P(R)2N(R('))2)2](2+). This "bottom-up" approach has allowed us to evaluate individual functional group and structural contributions to electrocatalysts for H2 oxidation and production. For instance, using amine, ether, and carboxylic acid functionalities in the outer coordination sphere enhances proton movement and results in lower catalytic overpotentials for H2 oxidation, while achieving water solubility in some cases. Amino acids with acidic and basic side chains concentrate substrate around catalysts for H2 production, resulting in up to 5-fold enhancements in rate. The addition of a structured peptide in an H2 production catalyst limited the structural freedom of the amino acids nearest the active site, while enhancing the overall rate. Enhanced stability to oxygen or extreme conditions such as strongly acidic or basic conditions has also resulted from an amino acid based outer coordination sphere. From the "top-down" approach, others have achieved water solubility and photocatalytic activity by associating this core complex with photosystem-I. Collectively, by use of this well understood core, the role of individual and combined features of the outer coordination sphere are starting to be understood at a mechanistic level. Common mechanisms have yet to be defined to predictably control these processes, but our growing knowledge in this area is essential for the eventual mimicry of enzymes by efficient molecular catalysts for practical use.